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Protective role of chrysin on thioacetamide-induced hepatic encephalopathy in rats
Chemico-Biological Interactions ( IF 5.1 ) Pub Date : 2018-11-28 , DOI: 10.1016/j.cbi.2018.11.021
Salma A. El-Marasy , Sally A. El Awdan , Reham M. Abd-Elsalam

Hepatic encephalopathy (HE) is a serious neuropsychiatric syndrome due to either acute or chronic hepatic failure. This study aimed to investigate the possible neuroprotective effect of chrysin, a natural flavenoid on thioacetamide (TAA)-induced hepatic encephalopathy in rats. Also the effect of chrysin on motor impairment, cognitive deficits, oxidative stress, neuroinflammation, apoptosis and histopathological damage was assessed. HE was induced in Wistar rats by intraperitoneal (i.p.) injection of TAA (200 mg/kg) for three alternative days. Normal and control groups received the vehicle for 21 days. Chrysin was administered orally for 21 days (25, 50, 100 mg/kg) and starting from day 17, rats received i.p. dose of TAA (200 mg/kg) at three alternative days. Then behavioral, biochemical, histopathological and immunohistochemical analyses were conducted. Chrysin improved TAA-induced motor incoordination as it reduced final falling latency time in rotarod test, ameliorated cognitive deficits in object recognition test (ORT) and attenuated serum ammonia, hepatic liver enzymes namely, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), reduced malondialdehyde (MDA), elevated reduced glutathione (GSH), reduced nuclear factor kappa B (NF-κB), tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) brain contents. Chrysin administration also reduced Toll-4 receptor (TLR-4) gene expression, caspase-3 protein expression, hepatic necrosis and astrocyte swelling. This study depicts that chrysin exerted neuroprotective effect in TAA-induced HE rats, evidenced by improvement of cognitive deficits, motor incoordination and histopathological changes such as astrocyte swelling and vacuolization; hallmarks in HE, via reducing hyperammonia, ameliorating hepatic function, in addition to its anti-oxidant, inactivation of TLR-4/NF-κB inflammatory pathway, and anti-apoptotic effects.



中文翻译:

菊花蛋白对硫代乙酰胺诱导的大鼠肝性脑病的保护作用

肝性脑病(HE)是由于急性或慢性肝衰竭导致的严重神经精神病综合症。这项研究旨在调查天然的黄酮类植物Chrysin对硫代乙酰胺(TAA)诱导的大鼠肝性脑病的可能的神经保护作用。还评估了菊花蛋白对运动障碍,认知障碍,氧化应激,神经炎症,细胞凋亡和组织病理学损害的影响。在Wistar大鼠中,通过腹膜内(ip)注射TAA(200 mg / kg)连续三天来诱导HE。正常和对照组接受了21天的车辆。每天口服21天(25、50、100 mg / kg)的菊花蛋白,并从第17天开始,在接下来的3天中,大鼠腹腔注射TAA(200 mg / kg)。然后是行为,生化,进行了组织病理学和免疫组化分析。菊花蛋白改善了TAA诱导的运动不协调性,因为它减少了在旋转脚架测试中的最终下降潜伏时间,减轻了对象识别测试(ORT)中的认知缺陷并减弱了血清氨,肝肝酶,即天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)减少丙二醛(MDA),减少谷胱甘肽(GSH),减少核因子κB(NF-κB),减少肿瘤坏死因子-α(TNF-α)和白介素-6(IL-6)的大脑含量。服用胰蛋白酶还降低了Toll-4受体(TLR-4)基因表达,caspase-3蛋白表达,肝坏死和星形胶质细胞肿胀。这项研究表明,Chrysin对TAA诱导的HE大鼠具有神经保护作用,这可以通过改善认知功能障碍来证明,运动失调和组织病理学变化,例如星形胶质细胞肿胀和空泡形成;除具有抗氧化作用,TLR-4 /NF-κB炎性途径失活和抗凋亡作用外,还可通过减少高氨血症,改善肝功能来实现HE的标志性功能。

更新日期:2018-11-28
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